A rare case of primary signet-ring adenocarcinoma of anorectal region in a young patient: Diagnostic challenges and therapeutic outcomes.

Key Clinical Message: Primary signet-ring cell carcinoma of the anal canal and rectum is an extremely rare and aggressive malignancy. The present case underscores the importance of considering primary signet-ring cell carcinoma in differential diagnoses for young patients with chronic anorectal symptoms. It highlights the need for a multidisciplinary treatment approach (including surgery, chemotherapy, and radiotherapy) and comprehensive follow-up for managing this challenging condition and improving long-term patient outcomes. Abstract: Primary signet-ring cell carcinoma of the anal canal and rectum is an exceedingly rare subtype of colorectal adenocarcinoma, often originating as an extension of rectal adenocarcinoma. This malignancy constitutes a small fraction of colorectal cancers and is scarcely reported in medical literature. We present the case of an 18-year-old male with a three-year history of progressively worsening hematochezia, anorectal pain, and defecation-associated prolapse. Initial conservative treatments failed, leading to further investigations that revealed a palpable, nodular anorectal mass. Imaging studies (including CT and MRI), and biopsy confirmed poorly differentiated adenocarcinoma with signet-ring cell morphology. The tumor exhibited extensive lymphovascular invasion and involved perirectal lymph nodes, and was staged as pT3, N2a. Immunohistochemical staining was positive for CK 7, CK 20, and SATB2, supporting the primary anorectal origin. The treatment regimen included initial diversion colostomies for symptom relief, followed by neoadjuvant chemotherapy with a modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen and concurrent chemoradiation with Xeloda. The patient subsequently underwent an abdominoperineal resection (APR), which confirmed the diagnosis and achieved curative resection. Postoperative complications included transient ileus and wound infection, which were managed with supportive care. This case underscores the diagnostic and therapeutic challenges posed by primary signet-ring cell carcinoma of the anorectal region, highlighting the need for a high index of suspicion and comprehensive diagnostic workup in atypical presentations. The multimodal treatment approach, incorporating surgery, chemotherapy, and radiotherapy, was crucial in managing this locally advanced tumor. The rarity and aggressiveness of this carcinoma necessitate a tailored treatment strategy to improve patient outcomes. Long-term follow-up, including regular imaging and surveillance, is vital for monitoring disease recurrence and evaluating treatment effectiveness.

Management of patients with reduced dihydropyrimidine dehydrogenase activity receiving combined 5-fluoruracil-/capecitabine-based chemoradiotherapy.

BACKGROUND: 5­Fluoruracil (5-FU) and its oral prodrug capecitabine are mainstays in combined chemoradiotherapy regimens. They are metabolized by dihydropyrimidine dehydrogenase (DPYD). Pathogenic variants of the DPYD gene cause a reduction in DPYD activity, leading to possibly severe toxicities. Therefore, patients receiving 5­FU-/capecitabine-based chemoradiotherapy should be tested for DPYD variants. However, there are limited clinical data on treatment adjustments and tolerability in patients with decreased DPYP activity receiving combined chemoradiotherapy. Therefore, a retrospective analysis of the toxicity profiles of patients with decreased DPYD activity treated at our center was conducted. MATERIALS AND METHODS: For all patients receiving 5­FU-/capecitabine-based chemo(radio)therapy at our department, DPYD activity was routinely tested. Genotyping of four DPYD variants (DPYD*2A, DPYD*13, c.2846A > T, and haplotype B3) was conducted according to the recommendation of the German Society for Hematooncology (DGHO) using TaqMan hydrolysis polymerase chain reaction (PCR; QuantStudy 3, Thermo FisherScientific, Darmstadt). DPYD variants and activity score as well as clinical data (tumor entity, treatment protocol, dose adjustments, and toxicity according to the Common Terminology Criteria for Adverse Events [CTCAE]) were assessed and reported. RESULTS: Of 261 tested patients, 21 exhibited DPYD variants, 18 of whom received chemoradiotherapy. All but one patient was treated for rectal or anal carcinoma. The observed rate of DPYD variants was 8.0%, and heterozygous haplotype B3 was the most common (5.75%). One patient exhibited a homozygous DPYD variant. DPYD activity score was at least 0.5 in heterozygous patients; chemotherapy dose was adjusted accordingly, with an applied dose of 50-75%. CTCAE grade 2 skin toxicity (50%) and grade 3 leukopenia (33.3%) were most common. One patient experienced a transient grade 4 increase in transaminases. All high-grade toxicities were manageable with supportive treatment and transient. No CTCAE grade 5 toxicities related to 5­FU administration were observed. CONCLUSION: With dose reduction in heterozygous patients, toxicity was within the range of patients without DPYD variants. Our clinical data suggest that dose-adapted 5­FU-/capecitabine-chemoradiotherapy regimens can be safely considered in patients with heterozygous clinically relevant DPYD variants, but that the optimal dosage still needs to be determined to avoid both increased toxicity and undertreatment in a curative setting.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

BACKGROUND: To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. METHODS: In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. RESULTS: We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). CONCLUSION: Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Gender-Related Aspects of Laryngeal Squamous Cell Carcinoma: A Retrospective Cohort Study.

OBJECTIVES: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender-based differences. DESIGN: Retrospective cohort study. SETTING: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status. PARTICIPANTS: Two hundred ninety-one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males. MAIN OUTCOME MEASURES: Disease-specific survival (DSS), overall survival (OS) and disease-free survival (DFS), as well as differences in disease characteristics and treatment modalities. RESULTS: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced-stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log-rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log-rank p = 0.017). No significant differences in DFS were observed (log-rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10-3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04-1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08-2.67; p = 0.023). CONCLUSIONS: Our findings suggest the importance of considering gender-specific factors in the management of laryngeal SCC.

A Multimodality Treatment Approach for the Management of Recurrent Cervical Cancer in an Elderly Female Patient: A Case Report.

Squamous cells in the cervix can develop into a type of cervical cancer. Cervical squamous cells are the cells that line the outside of the cervix. These thin, flat cells have a striking resemblance to fish scales under a microscope. Squamous cell carcinomas (SCCs) are the most common type of cervical cancer. We report the case of a 60-year-old woman with SCC devoid of a family history of cancer or related diseases. Following a biopsy confirming SCC, the patient's contrast-enhanced computed tomography scan revealed a somewhat enlarged cervix along with a white discharge per vagina. The patient underwent a Wertheim hysterectomy and was diagnosed with microinvasive SCC, adenomyosis, and negative lymph nodes. Two years after being free from disease, the issue reappeared even with routine follow-ups. The patient underwent six rounds of chemotherapy, followed by chemoradiation and interstitial brachytherapy. The multimodality therapy method applied to an aged female patient experiencing recurrent SCC of the cervix is demonstrated in this case study. It underlines how crucial regular follow-ups and multimodal therapy are to control recurrent cervical cancer.

Short- and Long-Term Outcomes in Elderly Patients with Resectable Esophageal Cancer: Upfront Esophagectomy Compared to Surgery after Neoadjuvant Treatments.

Background/Objectives: Despite the increased incidence of esophageal cancer (EC) in elderly people, there are no clear guidelines for its treatment in these patients. The aim of this study was to compare the outcomes of patients ≥ 75 years with resectable EC, receiving either upfront esophagectomy or neoadjuvant treatment. Methods: We retrospectively identified 127 patients with resectable EC ≥ 75 years who underwent esophagectomy between January 2000 and December 2022 at our Clinic in the University Hospital of Padova. The included patients were stratified into two groups: patients undergoing upfront esophagectomy (SURG group) and patients receiving neoadjuvant treatment (NAT group). Results: There were no statistically significant differences in OS (p = 0.7708), DFS (p = 0.7827) and cancer-related survival (p = 0.0827) between the SURG and the NAT group, except for the OS of EAC with stage III-IV, where the NAT group experienced a significant benefit in OS (p = 0.0263). When comparing the two groups, patients receiving neoadjuvant treatment experienced a significantly higher rate of postoperative complications (p = 0.0266). At univariate analysis, neoadjuvant therapy was the only variable strongly associated with postoperative morbidity (p = 0.026). Conclusions: Considering the unique characteristics of elderly patients, the choice of a multimodal approach should be tailored to each case in a multidisciplinary setting and balanced with a potential higher risk of postoperative complications, as well as potential toxicity related to chemoradiation and reduced life expectancy.

Ibuprofen/acetaminophen fixed-dose combination as an alternative to opioids in management of common pain types.

Opioids are frequently used first line to manage acute pain in a variety of settings; however, the use of nonprescription analgesics for acute pain is recognized by experts as a practical and effective opioid-sparing strategy. Variations in dosages and formulations and a lack of standardization in reporting clinical data hinder the awareness of nonprescription treatments and recommendation of their use before opioids and other prescription options. A fixed-dose combination (FDC) of two common nonprescription analgesics, ibuprofen (IBU) and acetaminophen (APAP), is an appealing alternative to opioids in acute pain settings with a range of potential benefits. This narrative review evaluates the evidence in support of IBU/APAP FDCs containing IBU (≤1200 mg/day) and APAP (≤4000 mg/day), the nonprescription maximum daily doses in Canada and the United States, as alternatives to opioids and as a means to reduce the need for rescue opioid medication in acute pain management. A literature search was performed to identify clinical studies that directly compared IBU/APAP FDCs with opioids or nonopioids and measured the need for opioid rescue therapy in acute pain. Across studies, IBU/APAP FDCs consistently demonstrated pain relief similar to or better than opioid and nonopioid comparators and reliably reduced the use of rescue opioids with fewer adverse events. Based on these data, healthcare clinicians should consider FDC nonprescription analgesics as a potential first-line option for the management of acute pain.

The growing trend of opioid-sparing treatment demands effective nonopioid pain management solutions. A fixed-dose combination (FDC) of ibuprofen and acetaminophen (IBU/APAP) has shown promise as an alternative to opioids in a range of pain management scenarios, but the available data are limited and can be difficult to compare across studies. In this review, the authors performed a comprehensive evaluation of the clinical studies that assessed the use of IBU/APAP FDCs as a means to prevent or decrease the use of opioids for patients with acute pain. In the included studies, IBU/APAP FDCs consistently and safely provided pain relief that could replace or reduce the need for opioids across a range of procedures. This manuscript can serve as a resource for healthcare clinicians when considering the use of IBU/APAP FDC treatments for acute pain management.

Acceptability of multimodal and multidisciplinary group-based program for chronic low back pain: a qualitative study.

BACKGROUND: The Programa d'Atenció Integral pels Pacients amb Dolor Crònic (PAINDOC) is a multimodal and multidisciplinary group-based program that integrates pain neuroscience education, mindfulness meditation, pain psychotherapy, Empowered Relief, and therapeutic exercise. It serves as a therapeutic option for individuals with chronic low back pain, providing them with comprehensive adaptive strategies for pain management. OBJECTIVE: This qualitative study explores participants' retrospective acceptability of the PAINDOC Program. METHODS: To ensure demographic variability and information power, a purposive sampling approach was applied. Twelve participants were interviewed through three focus groups, supplemented with four individual semi-structured interviews. Data was analyzed using reflexive thematic analysis and evaluated based on the Therapeutic Framework of Acceptability. RESULTS: Participants provide positive feedback regarding active pain coping strategies and improved self-management. While certain aspects of the Program were more emphasized, participants integrated tools from all components. Strategies included pain reconceptualization, positive self-talk, or problem-solving. The Program's ethicality was closely linked to individual values and may also be influenced by time constraints of certain program elements, the immediate effects of specific approaches, participant perceptions, and individual preferences. CONCLUSIONS: The findings provide valuable insights into the acceptability of the PAINDOC Program, guiding future improvements and the development of similar interventions.

Multidisciplinary approaches to chronic pain management have been explored and are recognized as an effective way to address the complexity of chronic pain conditions. These approaches often involve the collaboration of healthcare professionals from various disciplines.Multimodal pain management programs typically combine various treatment modalities, including physical therapy, cognitive-behavioral therapy, medication, and exercise.Studies have shown that multidisciplinary and multimodal interventions can be effective in reducing pain intensity, improving physical function, and enhancing quality of life in chronic low back pain patients. What does this study add? The multidisciplinary and multimodal group-based PAINDOC Program is acceptable for chronic low back pain patients.Participants noted the effectiveness of the program in helping them adopt active pain coping strategies and improve self-management.The ethicality of the multimodal Program depends on individual personal value systems, as certain program components may be less suitable for some participants.There might be some barriers to program adherence, including limited available time, the higher physical demands of exercise, the immediate effects of certain approaches, participants' perceptions, and individual needs and preferences.

Changes in tryptophan breakdown associated with response to multimodal treatment in depression.

Background: Research on depression showed that dysregulations in tryptophan (TRP), kynurenine (KYN), and its KYN pathway metabolites are key aspects in the development and maintenance of depressive symptoms. In our previous reports, we described sex-specific changes in TRP breakdown as well as changes in KYN and KYN/TRP in association with treatment response and inflammatory and metabolic parameters. However, results of treatment effects on KYN pathway metabolites as well as how pathway changes are related to treatment response remain sparse. Objective: We investigated potential changes of KYN and KYN pathway metabolites in association with therapeutic response of individuals with depression during a six-week multimodal psychiatric rehabilitation program. Methods: 87 participants were divided into treatment responders and non-responders (48 responders, 39 non-responders; 38 male, 49 female; M age = 51.09; SD age = 7.70) using scores of psychological questionnaires. KYN pathway metabolites serum concentrations as well as their ratios were collected using high performance liquid chromatography. Changes over time (time of admission (t1) vs. time of discharge (t2)) were calculated using repeated measure analyses of (co)variance. Results: Non-responders exhibited higher levels of 3-Hydroxyanthralinic acid (3-HAA), nicotinic acid (NA), and 3-HAA/KYN, independently of measurement time. NA levels decreased, while 3-HAA levels increased over time in both groups, independently of treatment response. 3-HK/KYN levels decreased, while KYN levels increased in non-responders, but not in responders over time. Discussion: The results indicate that some compounds of the KYN pathway metabolites can be altered through multimodal long-term interventions in association with treatment response. Especially the pathway degrading KYN further down to 3-HAA and 3-HK/KYN might be decisive for treatment response in depression.

Undifferentiated embryonal sarcoma of the liver in pediatric patients: a single-institution retrospective case series.

Background: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and highly aggressive malignancy predominantly affecting children and adolescents. Managing UESL is particularly intricate due to its aggressive nature and the limited array of treatment options available. This study is dedicated to elucidating the efficacy of a multimodal therapeutic strategy in the successful management of UESL. Case Description: Four pediatric patients (two males, two females; aged 6-11 years) diagnosed with UESL were treated at the Children's Hospital of Nanjing Medical University between November 2019 and June 2023. Surgical resection with lymph node dissection achieved complete primary tumor eradication. Adjuvant chemotherapy tailored to each patient's needs was followed by localized radiation therapy. After 9-42 months of follow-up, one patient who did not undergo immediate radiotherapy experienced a relapse. Following a second operation coupled with radiotherapy, the patient achieved complete remission, and mirroring the status of the other three patients who are now presently in remission. The overall cohort exhibited commendable tolerance to the treatment regimen, with manageable chemotherapy-related toxicities. Conclusions: This case series suggests that implementing a standardized protocol of resection, followed by adjuvant chemotherapy and radiation, can lead to favorable outcomes in pediatric patients diagnosed with UESL. Nevertheless, the need for comprehensive large-scale studies is imperative to substantiate the effectiveness of this approach.

A Rare Case of Rhabdosarcoma on the Upper Pole of the Kidney.

Rhabdomyosarcoma arising from the upper pole of the kidney is an exceedingly rare occurrence, with only a few documented cases reported in the literature. Here, we present a case of a one-year-old Indian male child diagnosed with rhabdomyosarcoma localized to the upper pole of the kidney. The patient presented with abdominal distension persisting for three days, and imaging studies revealed a mass consistent with renal sarcoma. Surgical excision was performed, followed by histopathological examination confirming the diagnosis of rhabdomyosarcoma. Despite aggressive management, the patient's prognosis remains guarded due to the disease's aggressive nature. This case highlights the importance of considering rhabdomyosarcoma in the differential diagnosis of renal masses, particularly in atypical locations. Early diagnosis and a multimodal treatment approach are crucial for optimizing outcomes in such rare cases.

Which Multimodal Physiotherapy Treatment Is the Most Effective in People with Shoulder Pain? A Systematic Review and Meta-Analyses.

The study aimed to determine if combined physiotherapy treatments offer additional benefits over exercise-only programs for shoulder pain and to identify the most effective combined treatment. A systematic review, registered in PROSPERO (CRD42023417709), and meta-analyses were conducted. Quality analysis was performed using the PEDro scale on randomized clinical trials published from 2018 to 2023. Twenty articles met the inclusion criteria. The most commonly used combination was exercise plus manual therapy, without being statistically superior to exercise alone. The meta-analysis indicated that combining exercise with low-level laser therapy (mean difference of -1.06, 95% CI: -1.51 to -0.60) and high-intensity laser therapy (mean difference of -0.53, 95% CI: -1.12 to 0.06) resulted in the greatest reduction in SPADI scores. Adding manual therapy provided limited additional benefit (mean difference of -0.24, 95% CI: -0.74 to 0.27). Progressive exercise with advice or telerehabilitation yielded modest improvements. The multimodal meta-analysis for DASH scores showed significant improvement (mean difference of -1.06, 95% CI: -1.51 to -0.60). In conclusion, therapeutic exercise is the cornerstone of shoulder pain treatment, with the addition of laser therapy showing substantial benefits. Manual therapy and educational interventions offer some benefits but are not consistently superior. More rigorous studies are needed.

Resilience in Rectal Cancer Treatment: Lessons from the COVID-19 Era in Czech Republic.

Introduction: The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. Methods: Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). Results: A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). Conclusion: Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.

Outcome improvement with chemotherapy and radiotherapy in primary, localized, radiation-associated angiosarcoma of the breast region: a retrospective case series analysis.

BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.

Temporal Trends and Cancer-Specific Mortality in Nonmetastatic Muscle-Invasive Urothelial Carcinoma of the Urinary Bladder Treated With Trimodal Therapy.

INTRODUCTION: Trimodal therapy (TMT) is guideline-recommended for the management of organ confined urothelial carcinoma of urinary bladder (UCUB). However, temporal trends in TMT use and cancer-specific mortality free-survival (CSM-FS) between historical TMT versus contemporary TMT have not been assessed. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified nonmetastatic UCUB patients with cT2-T4aN0-N2 treated with TMT, defined as the combination of transurethral resection of bladder tumor, chemotherapy and radiotherapy. Temporal trends described TMT use over time. Subsequently, patients were divided between historical (2004-2012) versus contemporary (2013-2020) cohorts. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM-FS. Separate analyses addressed patients with organ confined (OC: cT2N0M0) versus nonorgan confined (NOC: cT3-4a and/or cN1-2) clinical stages. RESULTS: Of 4,097 assessable UCUB TMT patients, 1744 (43%) were treated in the historical period (2004-2012) versus 2353 (58%) in the contemporary period (2013-2020). TMT use increased over time in OC patients (EAPC:+3.4%, P < .001), as well as in NOC (EAPC:+2.7%, P < .001). In OC stage, median CSM-FS was 55.3% in historical versus 49.0% in contemporary patients (HR:0.75, P < .001). Similarly, in NOC stage, 5-year median CSM-FS was 43.0% in historical versus 32.8% in contemporary patients (HR:0.78, P = .01). CONCLUSION: TMT rates have increased over time in both OC and NOC patients. Contemporary TMT patients benefit of better cancer-specific survival. Interestingly, this benefit applies equally to OC and NOC TMT-treated patients.

[Rehabilitation for patients with chronic pruritus]. / Rehabilitation bei Patienten mit chronischem Pruritus.

BACKGROUND: For a long time, chronic pruritus was considered difficult to treat. Modern therapy options and detailed guidelines have created new opportunities for patients to improve their quality of life. However, due to the complexity of the disease, the need for multimodal treatment remains. OBJECTIVES: This article aims to investigate whether dermatological rehabilitation offers additional benefits to those affected and whether it should therefore be part of the treatment concept for chronic pruritus. METHODS: After introduction of the pruritus program of a rehabilitation clinic, a prospective study is presented that focuses on the patient-relevant benefits of therapy. It used standardized questionnaires to record pruritus intensity, the presence of depression, anxiety, itch-related limitations, and quality of life in patients with chronic pruritus before and after rehabilitation. RESULTS: Of the patients surveyed, 91.7% achieved a patient-relevant benefit through rehabilitation. Pruritus intensity, depression, anxiety, itch-related limitations, and restrictions on quality of life decreased significantly. Almost half of all participating patients had been initially diagnosed more than 10 years ago. CONCLUSIONS: Dermatological rehabilitation with a multimodal concept for the treatment of chronic pruritus can help affected patients and should be part of the therapy concept. This should be done as early as possible before the disease progresses over a long period of time and makes treatment more difficult.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Successful Multimodal Treatment of Intracranial Growing Teratoma Syndrome with Malignant Features.

Molecular analysis of the growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

[Rational timepoint of medical rehabilitation in chronic tinnitus : Applying for rehabilitation options for a chronic course]. / Sinnvoller Zeitpunkt medizinischer Rehabilitation bei Tinnitus : Beantragung von Rehabilitationsmöglichkeiten bei chronischem Verlauf.

Chronic tinnitus is a common symptom of the auditory system. A causal therapy does not yet exist. The recommended treatment includes expert counseling, psychotherapeutic interventions, particularly cognitive behavioral therapy, and measures to improve hearing. The treatment modules are multimodal and can be combined individually. Depending on the severity of the different disease dimensions (tinnitus and comorbidities), a rehabilitative approach may be useful for maintaining health and occupational ability. In addition to a thorough and well-founded diagnosis and counseling, specific cognitive behavioral therapy and non-specific psychotherapeutic interventions (mindfulness/relaxation) on an individual or group basis, physiotherapy, and exercise, as well as auditory rehabilitation measures (hearing aids, auditory therapy) in the context of multimodal therapy approaches are necessary.

International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.